Effect of natural cocoa powder consumption on blood lipids, inflammatory and metabolic biomarkers in sickle cell patients at the Ghana Institute of Clinical Genetics (GICG), Korle Bu Teaching Hospital

开始日期2024-02-05

申办/合作机构-

NCT05545865 / RecruitingN/AIIT

Preclinical Trials to Determine the Range of Chardonnay Mark Intake for Improved Metabolic and Vascular Response.

This study aims to obtain data on the potential influence of Vine to Bar product(s) containing Chardonnay marc on cardiometabolic health. These initial studies will inform the design and timing of data collection for future dietary intervention trials that will examine the influence of Chardonnay marc intake on outcomes/biomarkers of both cardiometabolic health and the gut microbiome. This includes collecting data on the potential differences in response to the products based on the unique food matrix for each of the products that will be tested. Moreover, as there is a paucity of data on the influence of cocoa flavanol intake on vascular function beyond 4 hours post intake, the response of the selected outcomes will be assessed after 6 hours of flavanol intake. This is a time point that captures the increased circulating presence of microbial derived flavanol metabolites.

开始日期2022-09-01

申办/合作机构

University of California, Davis

NCT04794530 / Recruiting临床3期IIT

COCOA Flavanols to Improve Walking Performance in PAD: the COCOA-PAD II Trial

Among people with peripheral artery disease (PAD) age 55 and older, the investigators will test the hypothesis that PAD participants randomized to cocoa flavanols will have greater improvement or less decline in six-minute walk distance at six-month follow-up, compared to those randomized to placebo. The study will randomize 190 participants with PAD age 55 and older to one of two groups for six months: cocoa flavanols vs placebo. Our primary outcome is change in six-minute walk distance at six-month follow-up. Secondary outcomes are Actigraph-measured physical activity, brachial artery flow-mediated dilation (FMD), gastrocnemius muscle biopsy measures of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, gastrocnemius muscle perfusion (measured by magnetic resonance imaging (MRI)) and gastrocnemius muscle characteristics (measured by muscle biopsy).
To achieve the specific aims, the study will randomize 190 participants age 55 and older with PAD to one of two groups: cocoa flavanols vs placebo. Participants will be followed for six months.

开始日期2021-11-19

申办/合作机构

Northwestern University

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100 项与可可黄烷醇相关的临床结果

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100 项与可可黄烷醇相关的转化医学

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100 项与可可黄烷醇相关的专利（医药）

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项与可可黄烷醇相关的文献（医药）

2024-02-01·Food research international (Ottawa, Ont.)

A synchrotron X-ray scattering study of the crystallization behavior of mixtures of confectionary triacylglycerides: Effect of chemical composition and shear on polymorphism and kinetics.

Article

作者: Elena Simone ; Michael Rappolt ; Holly Ewens ; Tom Rutherford ; Stephanie Marty Terrade ; Francesca Giuffrida ; Cynthia Marmet

Cocoa butter equivalents (CBE) are mixtures of triglycerides from multiple sources (e.g., sunflower oil, mango kernel and sal), which resemble cocoa butter (CB) in both physical and chemical properties. Despite being widely used to replace CB in chocolate products, the crystallization behavior of many CBEs is still poorly understood. The aim of this work was to develop a fundamental understanding, at the molecular level, of the crystallization behavior of selected CBEs, and compare it with that of CB. Chromatography was used to determine the composition of CBEs, in terms of fatty acids and triacylglycerides (TAGs), while their thermodynamic behavior and crystallization kinetics were studied using polarized microscopy, differential calorimetry and three different synchrotron X-ray scattering setups. CBEs of different origin and chemical composition (e.g., different ratios of the main CB TAGs, namely POP, SOS and POS) crystallized in different polymorphs and with different kinetics of nucleation, growth and polymorphic transformation. SOS rich CBEs presented showed more polymorphs than CB and POP rich samples; whereas, CBEs with high concentration of POP showed slow kinetic of polymorphic transformation towards the stable β(3L) form. Additionally, it was observed that the presence of small amounts (<1% w/w) of specific TAGs, such as OOO, PPP or SSS, could significantly affect the crystallization behavior of CBEs and CBs in terms of kinetics of polymorphic transformation and number of phases detected (multiple high melting β(2L) polymorphs were identified in all samples studied). Finally, it was found that, regardless of the CBE composition, the presence of shear could promote the formation of stable β polymorphs over metastable β' and γ forms, and reduced the size of the crystal agglomerates formed due to increased secondary nucleation.

2024-01-29·Bioscience, biotechnology, and biochemistry

Effects of flavanols and procyanidins-rich cocoa consumption on metabolic syndrome: an update review (2013 to 2023).

Article

作者: Sharvintha Salaish Kumar ; Abbe Maleyki Mhd Jalil ; Napisah Hussin ; Zulfitri 'Azuan Mat Daud ; Amin Ismail

Studies indicated that cocoa-based products effectively mitigate the risks associated with metabolic syndrome (MetS), however, the effect varies based on cocoa types, dosages, and study durations. This review aimed to determine the flavanol-rich cocoa consumption on MetS outcomes within the last decade (2013 to 2023), adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seven randomised-controlled trials (RCT) used cocoa-based products containing 0.3 to 1680 mg flavanol monomers and 3.5 to 1270 mg procyanidins. Cocoa-based products beneficially reduced glycemic response, blood pressure and lipid profiles. However, this review highlights little evidence pinpointing the best cocoa products type and required dosage for the observed effects. Further intervention aiming to improve MetS should justify the selection and concentration of flavanols (monomers and procyanidins). A robust study design should consider registering the trials before study commencement, consider multicenter RCT trials, and adjust for potential covariates that might 'masked' the outcomes.

2024-01-08·American journal of physiology. Cell physiology

Cocoa flavanols, Nrf2 activation, and oxidative stress in peripheral artery disease: Mechanistic findings in muscle based on outcomes from a randomized trial.

Article

作者: Ahmed Ismaeel ; Mary M McDermott ; Jai K Joshi ; Jada C Sturgis ; Dongxue Zhang ; Karen J Ho ; Robert Sufit ; Luigi Ferrucci ; Charlotte A Peterson ; Kate Kosmac

The pathophysiology of muscle damage in peripheral artery disease (PAD) includes increased oxidant production and impaired antioxidant defenses. Epicatechin (EPI), a naturally occurring flavanol, has antioxidant properties which may mediate the beneficial effects of natural products such as cocoa. In a Phase II randomized trial, a cocoa-flavanol rich beverage significantly improved walking performance compared to placebo in people with PAD. In the present work, the molecular mechanisms underlying the therapeutic effect of cocoa flavanols were investigated by analyzing baseline and follow-up muscle biopsies from participants. Increases in nuclear factor erythroid 2-related factor 2 (Nrf2) target antioxidants heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) in the cocoa group were significantly associated with reduced accumulation of central nuclei, a myopathy indicator, in Type II muscle fibers (p=0.017 and p=0.023, respectively). Protein levels of the mitochondrial respiratory complex III subunit, cytochrome b-c1 complex subunit 2 (UQCRC2), were significantly higher in the cocoa group compared to placebo (p=0.032) and increases in UQCRC2 were significantly associated with increased levels of Nrf2 target antioxidants HO-1 and NQO1 (p=0.001 and p=0.035, respectively). Exposure of non-PAD human myotubes to ex vivo serum from patients with PAD reduced Nrf2 phosphorylation, an indicator of activation, increased hydrogen peroxide production and oxidative stress, and reduced mitochondrial respiration. Treatment of myotubes with EPI in the presence of serum from PAD patients increased Nrf2 phosphorylation and protected against PAD serum-induced oxidative stress and mitochondrial dysfunction. Overall, these findings suggest that cocoa flavanols may enhance antioxidant capacity in PAD via Nrf2 activation.

项与可可黄烷醇相关的新闻（医药）

2024-01-02

·药研发

【药研发0103】新元素急性痛风新药获批Ⅰ期临床 | 江苏瑞科带状疱疹疫苗早期临床积极...

「本文共：16条资讯，阅读时长约：3分钟」今日头条新元素急性痛风新药获批Ⅰ期临床。新元素医药抗炎症领域小分子创新药ABP-745获FDA批准开展I期临床，拟评估用于治疗急性痛风的安全性与初步疗效。该新药目前已在国内报IND。值得一提的是，该公司也正在开发一种口服小分子URAT1抑制剂ABP-671用于治疗慢性痛风，该药物旨在降低患者的血尿酸水平，目前正在全球范围内开展关键性多中心临床试验。国内药讯1.阿斯利康RSV长效单抗中国获批上市。阿斯利康长效呼吸道合胞病毒（RSV）抗体Nirsevimab注射液获国家药监局批准上市，用于预防新生儿和婴儿由呼吸道合胞病毒（RSV）引起的下呼吸道感染（LRTI）。这是全球唯一、可广泛应用于婴幼儿群体的单剂次被动免疫制剂。在临床试验中，nirsevimab可降低79.5%（p<0.0001）的婴幼儿因RSV感染导致的LRTI风险。2.百济神州PD-1单抗获批一线治疗肝癌。百济神州PD-1抑制剂替雷利珠单抗注射液（商品名：百泽安）获国家药监局批准用于治疗一线不可切除或转移性肝细胞癌患者。在全球III期RATIONALE 301研究（NCT03412773）中，替雷利珠单抗与索拉非尼对照组相比达到总生存期（OS）非劣效性的治疗效果（中位OS：15.9个月vs14.1个月）。3.君实PD-1单抗新适应症获批上市。君实生物PD-1抑制剂特瑞普利单抗获国家药监局批准新适应症，联合化疗用于可切除III期非小细胞肺癌（NSCLC）的围手术期治疗和单药用于辅助治疗后巩固治疗。在III期临床（Neotorch）中，与单纯化疗相比，特瑞普利单抗的治疗方案可显著延长患者无事件生存期，使疾病复发、进展或死亡风险降低达60%（HR=0.40，95%CI：0.277-0.565，双侧P<0.0001）。4.恒瑞HER3-ADC获肺癌快速通道资格。恒瑞医药靶向HER3的抗体偶联药物（ADC）SHR-A2009获FDA授予快速通道资格，用于治疗经三代EGFR酪氨酸激酶抑制剂和含铂化疗后疾病进展的EGFR突变的转移性非小细胞肺癌。SHR-A2009可特异性结合肿瘤细胞表面上的HER3，进而被内吞至细胞内水解释放游离毒素，杀伤肿瘤细胞。在国际I期临床中，SHR-A2009已显示出具有良好的抗肿瘤活性和安全性。5.信达GLP-1R/GCGR激动剂上肥胖III期临床。信达生物GLP-1R/GCGR双重激动剂玛仕度肽9mg (IBI362) 用于中国肥胖受试者减重的III期临床（GLORY-2）完成首例受试者给药。Ⅱ期临床48周治疗数据显示，玛仕度肽（9mg）治疗较安慰剂使患者体重降幅达到18.6%（减重17.8公斤）；该组减重超过5%和10%的患者比例分别达到83.7%和69.8%。这也是玛仕度肽开展的第四项III期临床研究。6.江苏瑞科带状疱疹疫苗早期临床积极。瑞科生物自主研发的新佐剂重组带状疱疹疫苗REC610在菲律宾首次人体（FIH）试验中获积极结果。REC610组接种后可诱导较强的gE特异性体液免疫和细胞免疫应答，免疫应答在两剂接种后30天达到高峰，其水平与Shingrix®（葛兰素史克）组相当，且在数值上高于Shingrix®组；REC610在老年及成年人群均可诱导较好的体液免疫和细胞免疫应答。此外，疫苗总体安全性良好。7.宜联生物c-Met靶向ADC授权罗氏。宜联生物宣布已与罗氏就其临床前期靶向间质表皮转化因子（c-Met）的下一代抗体偶联药物（ADC）YL211达成合作和许可协议，授予后者在全球范围内的开发、制造和商业化的独家权益。根据协议，宜联生物将获得首付款及近期里程碑付款5000万美元，约10亿美元的开发、注册和商业化潜在里程碑付款，以及产品销售净额的梯度特许权使用费。国际药讯1.FDA发布细胞和基因治疗产品的效力保证指南草案。FDA日前发布“细胞和基因治疗产品的效力保证”的指南草案，就制定基于科学和风险的策略以帮助确保人用细胞和基因治疗（CGT）产品的效力提供建议。FDA建议企业在产品生命周期的所有阶段使用质量风险管理来评估产品效力的风险，并将这些风险降低到可接受的水平。FDA 建议企业在为产品设计效力保证策略时考虑下述概念：质量目标产品概况（QTPP）、控制策略、关键质量属性（CQA）、关键过程参数（CPP），以及风险评估和风险降低。2.现货型细胞免疫疗法乳癌临床积极。BriaCell公司现货型细胞免疫疗法Bria-IMT（SV-BR-1-GM）治疗晚期转移性乳腺癌的临床试验结果积极。该项研究评估Bria-IMT单药以及与免疫检查点抑制剂（CPI）联合用药的治疗效果。数据显示，Bria-IMT治疗使71%患者（n=5/7）CNS病变显著缓解；所有乳腺癌亚型患者均观察到CNS转移肿瘤消退。此前，Bria-IMT已获FDA授予快速通道资格。3.JAK抑制剂治疗1型糖尿病Ⅱb期临床积极。礼来与Incyte开发的JAK抑制剂巴瑞替尼（Olumiant）一线治疗具有临床C肽分泌功能的1型糖尿病者的Ⅱb期临床积极结果发表在NEJM上。干预48周后，巴瑞替尼组混合餐刺激的C肽平均水平中位数0.65 nmol/(L·min)，显著高于安慰剂组0.43 nmol/(L·min)；校正后的平均组间差异为0.13（P=0.001）；两组日均胰岛素用量分别为0.41 U/(kg·d)和0.52 U/(kg·d)，两组均未发生严重不良事件。4.O药联合LAG-3抗体结直肠癌Ⅲ期临床失败。百时美施贵宝宣布将终止PD-1抑制剂纳武利尤单抗Opdivo联合LAG-3抗体relatlimab（Opdualag）治疗转移微卫星稳定（MSS）结直肠癌（CRC）的III期RELATIVITY-123临床。与瑞戈非尼或曲氟尿苷替匹嘧啶相比，O药和relatlimab组合未达到主要研究终点。该组合治疗其它类型肿瘤的试验仍继续进行。Relatlimab是首款获FDA批准的LAG-3抗体。5.可可提取物补充剂或对老人认知有好处。由布莱根妇女医院开展、评估每天服用可可提取物或普通复合维生素补充剂是否会降低患心脏病、中风、癌症和其他重要健康问题的风险的临床COSMOS研究成果在线发表在The American Journal of Clinical Nutrition期刊上。为期两年的针对认知能力的评估结果显示，服用每天含有500毫克可可黄烷醇的可可提取物补充剂对习惯性饮食质量较低的老年人的认知能力有好处。6.AI模型加速发现新型候选抗生素。麻省理工学院James Collins教授团队日前在国际期刊Nature上发表"Discovery of a structural class of antibiotics with explainable deep learning"研究论文。该研究利用人工智能（AI）和可解释的深度学习模型，从超过1200万种化合物中识别出一种革命性的新型抗生素类型，可以杀死临床上常见的超级细菌——耐甲氧西林金黄色葡萄球菌（MRSA）。而且，这些化合物对人类细胞的毒性很低。医药热点1.上海首批32家社区标准化口腔诊室建成。近日，上海首批32家社区标准化口腔诊室建成，旨在提升社区口腔服务能级，满足更多居民“家门口”多层次社区口腔诊疗和保健服务需求。下一步，在继续巩固社区口腔诊室建设成效的基础上，上海市将继续推进社区标准化口腔的建设，至2030年末，基本实现社区标准化口腔诊室功能全覆盖，社区口腔诊疗、保健服务全面提升能级。2.复旦附属眼耳鼻喉科医院浦江院区二期项目启动。12月27日，复旦大学附属眼耳鼻喉科医院浦江院区二期项目正式启动。浦江院区二期工程位于闵行区江月路2600号，占地100亩。在一期350张住院床位基础上，新增住院床位150张，进一步改善医疗就医环境与条件。此外，项目在设计中引入纵贯南北的“医疗街”，将整个院区有机整合，各功能区结构明确、流程清晰、独立成区，又互相紧密联系。评审动态 1. CDE新药受理情况（12月30日) 2. FDA新药获批情况（北美12月27日）股市资讯上个交易日 A 股医药板块 +0.42%涨幅前三跌幅前三生物谷 +8.56% 博瑞医药-7.03%诺思兰德+7.51% 迈威生物-5.29%济川药业+5.95% 昊海生科-4.89%【普利制药]收到美国食品药品监督管理局(以下简称“FDA”)签发的创新药注射用PLAT001的药物临床试验批件。产品为注射用PLAT001，拟用于治疗胰腺癌等晚期或转移性实体瘤患者，IND号为156926。【君实生物]特瑞普利单抗注射液(商品名:拓益®，产品代号:JS001)，用于可切除IIIA-IIB期非小细胞肺癌的成人患者的新适应症上市申请获得批准，是我国首个、全球第二个获批的肺癌围手术期疗法。【益方生物]于近日收到国家药品监督管理局核准签发的《受理通知书》，公司产品格舒瑞昔片用于既往经一线系统治疗后疾病进展或不可耐受的、并且经检测确认存在KRAS G12C突变的局部晚期或转移性非小细胞肺癌的治疗的新药上市申请获得受理。- The End -戳“阅读原文”，了解更多医药研发及股市资讯。

临床3期快速通道临床1期疫苗临床2期

2023-12-28

·生物谷

AJCN | 临床试验表明可可提取物补充剂对饮食质量较低的老年人的认知有好处

可可提取物（cocoa extract）对认知能力有潜在的保护作用，但针对老年人的随机临床试验结果并不一致。在一项名为“可可补充剂和多种维生素结果研究（Cocoa Supplement and Multivitamin Outcomes Study, COSMOS）”的随机临床试验中，一项针对认知能力的新研究表明，服用每天含有 500 毫克可可黄烷醇的可可提取物补充剂对那些在参加这项临床研究时习惯性饮食质量较低的老年人的认知能力有好处。不过，在这项临床研究开始时已经拥有健康饮食模式的参与者中，并没有发现认知方面的益处。这项临床研究纳入了 573 名老年人，这些参与者接受了详细的认知测试。相关研究结果于2023年12月7日在线发表在The American Journal of Clinical Nutrition期刊上，论文标题为“Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial”。为期两年的详细神经心理学评估结果显示，与安慰剂相比，每天补充可可提取物对整体或特定领域的认知功能没有总体益处。不过，二次分析表明，饮食质量差的参与者服用可可提取物补充剂对认知功能有好处。这项临床研究是在亲自参加详细认知测试的 COSMOS 参与者中进行的，它的研究结果与来自早先的一项通过互联网对单独招募的一组 COSMOS 参与者进行了基于网络的认知评估的研究（PNAS, 2023, doi:10.1073/pnas.2216932120）的结果一致。COSMOS 是一项由研究者发起的大规模长期临床试验，由布莱根妇女医院领导。全美 21000 多名老年女性和男性参加了这项随机、双盲、安慰剂对照研究，以测试每天服用可可提取物或普通复合维生素补充剂是否会降低患心脏病、中风、癌症和其他重要健康问题的风险。对 COSMOS 数据的分析会持续揭示补充剂与人类健康之间的联系。参考资料：Chirag M. Vyas et al. Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial. The American Journal of Clinical Nutrition, 2023, doi:10.1016/j.ajcnut.2023.10.031.Cocoa Extract Supplement Found to Have Benefits for Cognition Among Older Adults with Lower Diet Qualityhttps://www.massgeneralbrigham.org/en/about/newsroom/press-releases/cocoa-extract-supplement-benefits-cognition-in-older-adults-with-lower-diet-quality本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

临床研究

2023-12-07

·Science Daily

Cocoa extract supplement may benefit cognition among older adults with lower diet quality

Researchers are reporting new evidence on the effectiveness of cocoa flavanol supplements for cognition. In a randomized controlled clinical trial of 573 people, the researchers found that older adults who had unhealthy diets and took daily cocoa extract supplements containing 500 mg/day of cocoa flavanols experienced cognitive benefits. Cognitive benefits however were not seen in participants who already had healthy dietary patterns. Cocoa extract has shown a potential protective effect on cognition but randomized clinical trials in older adults have had inconsistent results. A new study of cognition in a randomized trial, known as the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS), suggests that taking cocoa extract supplements containing 500 mg per day of cocoa flavanols had cognitive benefits for older adults who had lower habitual diet quality at the time of enrollment in the study. However, cognitive benefits were not found among participants who already had healthy dietary patterns at the start of the study. The study, conducted by researchers at Mass General Brigham, included 573 older adults who underwent detailed, in-person cognitive testing and is published online in The American Journal of Clinical Nutrition. Results from detailed neuropsychological assessments given over two years showed that daily cocoa extract supplementation, compared to placebo, had no overall benefits for global or domain-specific cognitive function. However, secondary analyses showed that participants with poor diet quality had cognitive benefits from taking the cocoa extract supplement. The findings from this study -- which was done among COSMOS participants who presented in-person for detailed cognitive testing -- are consistent with the results from an earlier study that used a web-based cognitive assessment given over the internet to a separately recruited set of COSMOS participants. COSMOS is an investigator-initiated large-scale, long-term clinical trial led by Brigham and Women's Hospital. More than 21,000 older women and men were enrolled across the United States to participate in this randomized, double-blinded, placebo-controlled study to test whether taking daily supplements of a cocoa extract or a common multivitamin reduces the risk for developing heart disease, stroke, cancer, and other important health outcomes. Analyses of the data from COSMOS continue to yield insights about the connections between supplements and human health. Funding statement: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is supported by an investigator-initiated grant from Mars Edge, a segment of Mars dedicated to nutrition research and products, which included infrastructure support and the donation of study pills and packaging. Pfizer Consumer Healthcare (now Haleon) provided support through the partial provision of study pills and packaging. COSMOS is also supported in part by grants AG050657, AG071611, EY025623, and HL157665 from the National Institutes of Health, Bethesda, MD. The Women's Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005. Neither Mars Edge nor Pfizer Consumer Healthcare provided input regarding data analyses, interpretation of results, or manuscript development.

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适应症	最高研发状态	国家/地区	公司
外周动脉闭塞性疾病	临床3期	美国更多	National Institute for Materials Science IAI 更多
原发性高血压	无进展	德国更多	Universität zu Köln 更多
内皮功能障碍	无进展	美国更多	The University of California, San Francisco 更多
妊娠期高血压	无进展	加拿大更多	Université Laval 更多
冠心病	无进展	美国更多	The University of California, San Francisco 更多

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


Pubmed	N/A	心脏衰竭	-	Flavanol-rich chocolate	繭顧廠觸簾蓋蓋網糧膚(積夢糧網築範構窪簾鏇) = 遞廠顧憲齋願鏇憲鹹窪遞夢獵廠膚觸襯積顧觸 (築積鬱觸鏇鏇網夢觸鬱 ) 更多	积极	2012-09-01
Pubmed	N/A	妊娠纹	210	Cocoa butter lotion	艱齋糧簾襯餘鹹憲獵構(構憲遞鹹製齋衊餘願憲) = 淵製餘遞構淵醖壓艱餘淵醖淵膚願範鏇淵艱顧 (鏇壓餘醖鹹糧製艱繭膚 )	不佳	2008-08-01
				Cocoa butter lotion (Placebo lotion)	艱齋糧簾襯餘鹹憲獵構(構憲遞鹹製齋衊餘願憲) = 憲獵淵餘鑰衊廠選鑰醖淵醖淵膚願範鏇淵艱顧 (鏇壓餘醖鹹糧製艱繭膚 )
CoCoA Study (Pubmed)	N/A	-	90	Cocoa flavanol (High Flavanol (HF))	憲齋窪淵鹽窪鏇窪夢糧(網構鑰簾構醖繭窪製範) = 夢願顧獵選衊衊醖蓋選齋製壓網壓構鏇鹹鹽繭 (膚餘鹹艱廠鹹繭製廠夢 ) 更多	积极	2015-03-01
				Cocoa flavanol (Intermediate Flavanol (IF))	憲齋窪淵鹽窪鏇窪夢糧(網構鑰簾構醖繭窪製範) = 鹽淵餘觸網願鬱簾願餘齋製壓網壓構鏇鹹鹽繭 (膚餘鹹艱廠鹹繭製廠夢 ) 更多
COSMOS-Mind (AAIC2022)	N/A	-	2,262	Cocoa extract	餘醖鹽蓋壓餘繭窪簾遞(構選鑰廠構蓋築網鏇選) = 觸壓醖簾鹽顧觸簾淵憲憲鏇遞鹽壓觸壓憲積壓 (鬱鑰淵築顧築遞窪範蓋, -0.02 ~ 0.08)	-	2022-09-14
COSMOS (Pubmed)	N/A	心血管疾病	-	cocoa flavanol supplementation (Cocoa extract supplement)	範艱範觸鹽廠範夢簾鑰(遞廠齋艱醖衊獵製製選): HR = 0.9 (95% CI, 0.78 ~ 1.02) 更多	积极	2022-03-16
				cocoa flavanol supplementation (Placebo)
ESC2019	N/A	-	38	cocoa flavanol supplementation	(醖積齋遞鹹顧衊構糧蓋) = 鑰獵淵觸繭淵築蓋餘鹹觸簾夢蓋願鏇廠製壓夢 (憲膚築鹽遞鬱糧鏇鑰壓 ) 更多	-	2019-09-02
				cocoa flavanol supplementation	(醖積齋遞鹹顧衊構糧蓋) = 衊壓窪糧憲廠鹽膚築鏇觸簾夢蓋願鏇廠製壓夢 (憲膚築鹽遞鬱糧鏇鑰壓 ) 更多